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A drug derived from bacteria in the soil on Easter Island can substantially extend the life span of mice, according to a study published online today in Nature. The drug, called rapamycin, is the first pharmacological agent shown to enhance longevity in a mammal, and it works when administered beginning late in life. Prior to this research, the only ways to increase rodents’ life span were via genetic engineering or caloric restriction–a nutritionally complete but very low-calorie diet.

Rapamycin is an antifungal compound already approved by the FDA as an immunosuppressive therapy to help prevent organ rejection in transplant patients. It is currently being tested in clinical trials for potential anticancer effects.

The drug had previously been shown to extend life span in invertebrates. “[This study is] exciting because it shows that it’s feasible to do this in a mammal,” says David Sinclair, codirector of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging at Harvard Medical School, who was not involved in the study. “Maybe 20 years from now we’ll look back at this study as a landmark that pointed the way to medicines of the future.”

In the new study, researchers found that rapamycin given to mice as a food supplement starting at 20 months of age–the equivalent of 60 years in humans–extended average life span by 9 percent in males and 13 percent in females. “It’s particularly exciting because it works so late in life to extend life span,” says Sinclair. “The fact that you can give a drug after 20 months of age in a mouse and still see a life-span extension is striking.”

The results were pooled from three independent studies–at Jackson Laboratory, in Bar Harbor, ME; the University of Texas Health Science Center, in San Antonio; and the University of Michigan, in Ann Arbor–and coordinated by the National Institute of Aging’s Interventions Testing Program (ITP). Rapamycin is the first success story to emerge from the ITP, which systematically evaluates anti-aging drug candidates for effectiveness in mice.

Experts believe it’s possible that rapamycin may tap into one of the same biochemical pathways as calorie restriction, an intervention long known to make mice live longer. While the drug was not as effective as a limited diet initiated early in life, it was far more powerful than a limited diet begun at the same advanced age. In ongoing studies, the researchers are testing different doses across a range of starting ages; an optimal combination may ultimately prove more potent than calorie restriction.

Stumbling across rapamycin’s late-in-life efficacy was a happy accident. Originally, the therapy was to begin at four months of age, but the amount of rapamycin required to sustain therapeutic blood levels turned out to be prohibitively expensive. By the time the researchers devised a solution–microencapsulating the drug in a polymer coating that only disintegrates in the intestine–the mice were much older.

The research team decided to go ahead with the study anyway, because if there was an effect with late-in-life administration, it would be particularly relevant for humans. Initiating a human treatment early in life would be less practical, and would expose patients to side effects for longer, says David Harrison, principal investigator of the Jackson Laboratory portion of the study. (Because the drug suppresses the immune system, patients taking it are more susceptible to dangerous infections.)

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Credit: Ian Sewell

Tagged: Biomedicine, aging, longevity, rapamycin, caloric restriction

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